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Pentoxifylline enhances the protective effects of hypertonic saline solution on liver ischemia reperfusion injury through inhibition of oxidative stress

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Hepatobiliary & Pancreatic Diseases International 2015年第2期14卷 194-200页

作者： Vinicius Rocha-Santos Estela RR Figueira Joel A Rocha-Filho Ana MM Coelho Rafael Soraes Pinheiro Telesforo Bacchella Marcel CC Machado Luiz AC D'Albuquerque Department of Gastroenterology Laboratory of Medical Investigations LIM37 Discipline of Liver and Gastrointestinal Transplantation Hospital das Clinicas University of Sao Paulo School of Medicine Discipline of Anesthesiology Hospital das Clinicas University of Sao Paulo School of Medicine Department of Gastroenterology Laboratory of Medical Investigations LIM37 Discipline of Liver and Gastrointestina Hospital das Clinicas University of Sao Paulo School of Medicinel Transplantation

BACKGROUND：Liver ischemia reperfusion（IR）injury triggers a systemic inflammatory response and is the main cause of organ dysfunction and adverse postoperative outcomes after liver ***（PTX）and hypertonic saline solution（HTS）have been identified to have beneficial effects against IR *** study aimed to investigate if the addition of PTX to HTS is superior to HTS alone for the prevention of liver IR ***： Male Wistar rats were allocated into three groups. Control rats underwent 60 minutes of partial liver ischemia, HTS rats were treated with 0.4 mL/kg of intravenous 7.5% NaCl 15 minutes before reperfusion, and HPTX group were treated with 7.5% NaC1 plus 25 mg/kg of PTX 15 minutes before reperfusion. Samples were collected after reperfusion for determination of ALT, AST, TNF-α, IL-6, IL-10, mitochondrial respiration, lipid peroxidation, pulmonary permeability and myeloperoxidase. RESULTS： HPTX significantly decreased TNF-α 30 minutes after reperfusion. HPTX and HTS significantly decreased ALT,AST, IL-6, mitochondrial dysfunction and pulmonary myelo- peroxidase 4 hours after reperfusion. Compared with HTS only, HPTX significantly decreased hepatic oxidative stress 4 hours after reperfusion and pulmonary permeability 4 and 12 hours after reperfusion. CONCLUSION： This study showed that PTX added the beneficial effects of HTS on liver IR injury through decreases of hepatic oxidative stress and pulmonary permeability.

关键词： pentoxifylline hypertonic saline solution hepatic oxidative stress ischemia reperfusion injury pulmonary permeability

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Polyethylene glycols: An effective strategy for limiting liver ischemia reperfusion injury

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World Journal of Gastroenterology 2016年第28期22卷 6501-6508页

作者： Gianfranco Pasut Arnau Panisello Emma Folch-Puy Alexandre Lopez Carlos Castro-Benítez Maria Calvo Teresa Carbonell Agustín García-Gil RenéAdam Joan Roselló-Catafau Department of Pharmaceutical and Pharmacological University of Padova and Veneto Institute of Oncology IRCCS 35128 Padova Italy Experimental Pathology Department Institute of Biomedical Research of Barcelona 08036 Barcelona Spain Centre Hepatobiliaire AP-HP Hopital Paul Brousse Inserm U935 Universite Paris-Sud Villejuif 75008 Paris France Unitat de Microscopia Optic Avancada CCiTUB Centre Cientifics i Tecnologics Faculty of Medicine University of Barcelona 08036 Barcelona Spain Physiology Department Faculty of Biology Universitat de Barcelona 08036 Barcelona Spain Hospital Clinico de Zaragoza 50009 Zaragoza Spain

Liver ischemia-reperfusion injury(IRI) is an inherent feature of liver surgery and liver transplantation in which damage to a hypoxic organ(ischemia) is exacerbated following the return of oxygen delivery(reperfusion). IRI is a major cause of primary nonfunction after transplantation and may lead to graft rejection, regardless of immunological considerations. The immediate response involves the disruption of cellular mitochondrial oxidative phosphorylation and the accumulation of metabolic intermediates during the ischemic period, and oxidative stress during blood flow restoration. Moreover, a complex cascade of inflammatory mediators is generated during reperfusion, contributing to the extension of the damage and finally to organ failure. A variety of pharmacological interventions(antioxidants, anticytokines, etc.) have been proposed to alleviate graft injury but their usefulness is limited by the local and specific action of the drugs and by their potential undesirable toxic effects. Polyethylene glycols(PEGs), which are non-toxic water-soluble compounds approved by the FDA, have been widely used as a vehicle or a base in food, cosmetics and pharmaceuticals, and also as adjuvants for ameliorating drug pharmacokinetics. Some PEGs are also currently used as additives in organ preservation solutions prior to transplantation in order to limit the damage associated with cold ischemia reperfusion. More recently, the administration of PEGs of different molecular weights by intravenous injection has emerged as a new therapeutic tool to protect liver grafts from IRI. In this review, we summarize the current knowledge concerning the use of PEGs as a useful target for limiting liver IRI.

关键词： ischemia reperfusion injury Polyethylene glycol Liver preconditioning Liver transplantation UW solution IGL-1 solution SCOT solution PEG rinse solution Machine perfusion

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Role of NF-kappaB in Liver ischemia reperfusion injury of Rats

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2003年第2期23卷 158-160页

作者：徐钧杨镇曾金华 Department of Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Wuhan 430030

To determine the role of NF-kappaB in ischemia reperfusion (I/R) injury of the rat liver, rats underwent partial hepatic ischemia and reperfusion. The left and median lobes of the liver were subjected to ischemia for 90 min followed by reperfusion for defined times. NF-kappaB activity was analyzed by electrophoretic mobility shift assay (EMSA). Semiquantitative reverse-transcriptase polymerase chain reaction was used to analyze TNF-α and ICAM-1 mRNA levels. Results showed during liver I/R injury, NF-kappaB activation was induced in a time dependent manner. NF-kappaB was activated within 1h and 2h after the initiation of reperfusion and decreased after 4 h. Messenger RNA expression of TNF-α and ICAM-1 were increased after the reperfusion of 2 h. It was concluded that during hepatic I/R injury, NF-kappaB was activated and could bind to special sequence in the promoters of budget genes, which can up-regulate the expression of TNF-α and ICAM-1 mRNA to result in ischemia reperfusion injury of the rat liver.

关键词： NF-kappaB liver ischemia reperfusion injury

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Combined postconditioning with ischemia and α7nAChR agonist produces an enhanced protection against rat myocardial ischemia reperfusion injury

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Chinese Medical Journal 2012年第2期125卷 326-331页

作者： XIONG Jun YUAN Yu-jing XUE Fu-shan WANG Qiang LI Shan LIAO Xu LIU Jian-hua CHEN Yi LI Rui-ping Department of Anesthesiology Tongren Hospital Capital Medical University Beijing 100730 China Department of Anesthesiology Plastic Surgery Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100144 China

Background Inflammation is one of important mechanisms for myocardial ischemia reperfusion injury （IRI）.ischemia postconditioning （IPOC） can protect the heart against IRI by inhibiting inflammation,but its cardioprotection is weaker than that of ischemia ***,the α7 subunit-containing nicotinic acetylcholine receptor （α7nAChR） agonist has shown anti-infiammatory effects in many diseases related to *** randomized controlled experiment was designed to evaluate whether combined postconditioning with IPOC and the α7nAChR agonist could produce an enhanced cardioprotection in a rat in vivo model of acute myocardial *** Fifty Sprague-Dawley rats were randomly divided into five equal groups：sham group,control group,IPOC group,α7nAChR agonist postconditioning group （APOC group） and combined postconditioning with IPOC and α7nAChR agonist group （combined group）.Hemodynamic parameters were recorded during the periods of ischemia and *** concentrations of troponin I （Tnl）,tumor necrosis factor α （TNF-α） and high-mobility group box 1 （HMGB-1） at 180 minutes after reperfusion were assayed in all *** the end of the experiment,the infarct size was assessed from excised hearts by Evans blue and triphenyl tetrazolium chloride *** As compared to the sham group,the infarct size in the other four groups was significantly increased,serum levels of Tnl,TNF-α and HMGB1 in the control group and TNF-α,HMGB1 in the IPOC group were significantly *** infarct size and serum concentrations of TNF-α,HMGB1 and Tnl in the IPOC,APOC and combined groups were significantly lower than those in the control *** compared to the IPOC group,the infarct size in the combined group was significantly decreased,serum concentrations of Tnl,TNF-α and HMGB1 in the APOC and combined groups were significantly *** the infarct size was significantly smaller in the combined group than in the APOC group,serum levels of TN

关键词： ischemia reperfusion injury ischemia postconditioning pro-informatory cytokines α7 subunit-containing nicotinic acetylcholine receptor pharmacologicalpostconditioning

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Nigella sativa relieves the deleterious effects of ischemia reperfusion injury on liver

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World Journal of Gastroenterology 2008年第33期14卷 5204-5209页

作者： Fahrettin Yildiz Sacit Coban Alpaslan Terzi Mustafa Ates Nurten Aksoy Hale Cakir Ali Riza Ocak Muharrem Bitiren Harran University Medical Faculty Department of General SurgerySanli Urfa 63300 Turkey Gaziantep University Medical Faculty Department of General SurgeryGaziantep 27310 Turkey Malatya State Hospital Department of General Surgery Malatya 44100 Turkey Harran University Medical Faculty Department of BiochemistrySanli Urfa 63300 Turkey Harran University Medical Faculty Department of Pathology Sanli Urfa 63300 Turkey

AIM: To determine whether Nigella sativa prevents hepatic ischemia-reperfusion injury to the liver. METHODS: Thirty rats were divided into three groups as sham (Group 1), control (Group 2), and Nigella sati-va (NS) treatment group (Group 3). All rats underwent hepatic ischemia for 45 min followed by 60 min period of reperfusion. Rats were intraperitoneally infused with only 0.9% saline solution in group 2. Rats in group 3 received NS (0.2 mL/kg) intraperitoneally, before isch-emia and before reperfusion. Blood samples and liver tissues were harvested from the rats, and then the rats were sacrifi ced. Serum aspartate aminotransfera-se (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were determined. Total antioxidant capacity (TAC), catalase (CAT), total oxida-tive status (TOS), oxidative stress index (OSI) and my-eloperoxidase (MPO) in hepatic tissue were measured. Also liver tissue histopathology was evaluated by light microscopy. RESULTS: The levels of liver enzymes in group 3 weresignifi cantly lower than those in the group 2. TAC in liver tissue was significantly higher in group 3 than in group 2. TOS, OSI and MPO in hepatic tissue were signifi cantly lower in group 3 than the group 2. Histo-logical tissue damage was milder in the NS treatment group than that in the control group. CONCLUSION: Our results suggest that Nigella sa-tiva treatment protects the rat liver against to hepatic ischemia-reperfusion injury.

关键词： Nigella sativa ischemia reperfusion injury Liver

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Protective Effects of Epigallocatechin-3-gallate on Intestinal ischemia reperfusion injury through Enhanced Activation of PI3K/Akt Pathway in Rats

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2015年第3期35卷 378-383页

作者：张玄何凡杨军陈知水 Key Laboratory of Organ Transplantation Ministry of Education and Ministry of Public Health Institute of Organ Transplantation Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Department of Nephrology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

Inflammation plays a critical role in intestinal ischemia reperfusion injury（IRI）. Epigallocatechin-3-gallate（EGCG） has been demonstrated to possess anti-inflammatory effect. This study examined the effect of EGCG on intestinal IRI and explored the possible mechanisms. Male Wistar rats were randomly divided into three groups： sham-operated group（Sham）, IRI control group（IRI） and IRI-EGCG group（EGCG）. Rats in IRI-EGCG group were administered dissolved EGCG in drinking water（0.4 mg/m L） for 14 days prior to IRI induction. A rat model of intestinal IRI was established by ligating the superior mesenteric artery（SMA） for 30 min, followed by reperfusion for 1 h. Intestinal histology, pro-inflammatory cytokines and mediators were examined and the effect of EGCG on PI3K/Akt signalling was assessed. EGCG significantly alleviated the pathological changes of the intestine and suppressed the IRI-induced up-regulation of TNF-α, IL-1 and IL-6 m RNA and protein expression in the serum and intestine. The mechanism might be that EGCG enhanced the activation of PI3K/Akt signalling pathway. In conclusion, the administration of EGCG can significantly mitigate the acute intestinal IRI in rats by enhancing the activation of PI3K/Akt signalling pathway to suppress inflammatory response and might be a promising alternative for the prevention or treatment of intestinal IRI in the clinical practice.

关键词： epigallocatechin-3-gallate intestine ischemia reperfusion injury PI3K/Akt inflammation

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Compared Serum Proteomics Study on Multiple Organ Dysfunction Following Intestinal ischemia reperfusion injury in Rabbit

Compared Serum Proteomics Study on Multiple Organ Dysfunctio...

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第八届海峡两岸心血管科学研讨会

作者： Hong-jie LI~1,Rui-li YAO~2,Xiu-li MEN~1,Xiao-yan KONG~1,Li-jun ZHAO~1 (1.Department of Pathophysiology of Hebei United University,Tangshan 063000,China 2.Tangshan Vocational Technical college,Tangshan 063000,China)

＜正＞Objective To explore the changes of serum proteomics in rabbit multiple organ dysfunction following intestinal ischemia reperfusion injury as well as its possible *** Multiple organ dysfunction （MODS） model in rabbits was induced by intestinal mesenteric artery occlusion for 4 h followed by reperfusion for 4 h,the changes in their organ function were *** model was considered successful if two or more organ system functional impairment *** samples were obtained from rabbits before and after the model of gut originated *** in samples were separated by two - dimensional electrophoresis （2 - DE）,the 2 - DE gels were stained by sliver staining and analyzed by PDQuest software 8.0 to compare the protein expression difference between the two *** spots with different expression level were subjected to matrix assisted laser desorption/ionization - time of flight - time of flight - mass spectrometry （MALDI - TOF - TOF - MS） for *** protein database was searched to further characterize the differential *** differential expression of haptoglobin and paraoxonase in serum before and after gut originated MODS was verified by western blot and *** 19 differential protein spots were screened out in the 2 - DE maps,11 proteins were up - regulated and 8 proteins were down - regulated in gut originated MODS rabbits’ s serum.4 of the 19 differential protein spots were selected for MALDI - TOF - TOF - MS study,and 2 of the 4 differential protein spots were identified satisfactorily as paraoxonase and haptoglobin, which content were increased in rabbits’ s serum after gut originated *** Serum proteomics of rabbit changed remarkably before and after gut originated MODS,paraoxonase and haptoglobin may be associated with the compensation after gut originated MODS.

关键词： serum proteomics multiple organ dysfunction ischemia reperfusion injury

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Morphological alterations and redox changes associated with hepatic warm ischemia-reperfusion injury

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World Journal of Hepatology 2017年第34期9卷 1261-1269页

作者： Rim Jawad Melroy D'souza Lisa Arodin Selenius Marita Wallenberg Lundgren Olof Danielsson Greg Nowak Mikael Bjornstedt Bengt Isaksson Division of Pathology Department of Laboratory Medicine Karolinska Institutet Department of Clinical Science Intervention and Technology (CLINTEC) Division of Surgery Karolinska Institutet Karolinska University Hospital Department of Clinical Science Intervention and Technology (CLINTEC) Division of Transplantation Surgery Karolinska Institutet Karolinska University Hospital

AIM To study the effects of warm ischemia-reperfusion(I/R) injury on hepatic morphology at the ultrastructural level and to analyze the expression of the thioredoxin(TRX)and glutaredoxin(GRX) *** Eleven patients undergoing liver resection were subjected to portal triad clamping(PTC). Liver biopsies were collected at three time points; first prior to PTC(baseline), 20 min after PTC(post-ischemia) and 20 min after reperfusion(post-reperfusion). Electron microscopy and morphometry were used to study and quantify ultrastructural changes, respectively. Additionally, gene expression analysis of TRX and GRX isoforms was performed by quantitative PCR. For further validation of redox protein status, immunogold staining was performed for the isoforms GRX1 and *** Post-ischemia, a significant loss of the liver sinusoidal endothelial cell(LSEC) lining was observed(P = 0.0003) accompanied by a decrease of hepatocyte microvilli in the space of Disse. Hepatocellular morphology was well preserved apart from the appearance of crystalline mitochondrial inclusions in 7 out of 11 patients. Postreperfusion biopsies had similar features as post-ischemia with the exception of signs of a reactivation of the LSECs. No changes in the expression of redox-regulatory genes could be observed at mR NA level of the isoforms of the TRX family but immunoelectron microscopy indicated a redistribution of TRX1 within the *** At the ultrastructural level, the major impact of hepatic warm I/R injury after PTC was borne by the LSECs with detachment and reactivation at ischemia and reperfusion, respectively. Hepatocytes morphology were well preserved. Crystalline inclusions in mitochondria were observed in the hepatocyte after ischemia.

关键词： Hepatic ischemia-reperfusion injury ischemia reperfusion injury Warm ischemia-reperfusion injury Glutaredoxins Thioredoxins Electron microscopy Oxidative stress Portal triad clamping

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Addition of ulinastatin to preservation solution promotes protection against ischemia-reperfusion injury in rabbit lung

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Chinese Medical Journal 2011年第14期124卷 2179-2183页

作者： XU Ming WEN Xiao-hong CHEN Shu-ping AN Xiao-xia XU He-yun Department of Anesthesiology First Affiliated Hospital Zhejiang University School of Medicine HangzhouZhejiang 310003 China Department of Anesthesiology Hangzhou First People's HospitalHangzhou Zhejiang 310006 China Department of Cardiothoracic Surgery First Affiliated Hospital Zhejiang University School of Medicine HangzhouZhejiang 310003 China

Background The composition of the lung preservation solution used in lung graft procurement has been considered the key to minimize lung injury during the period of ischemia. Low-potassium dextran glucose （LPDG）, an extracellular-type solution, has been adopted by most lung transplantation centers, due to the experimental and clinical evidences that LPDG is superior to intracellular-type solutions. Ulinastatin has been shown to attenuate ischemia-reperfusion （I/R） injury in various organs in animals. We supposed that the addition of ulinastatin to LPDG as a flushing solution, would further ameliorate I/R lung injury than LPDG solution *** Twelve male New Zealand white rabbits were randomly divided into 2 groups. Using an alternative in situ lung I/R model, the left lung in the control group was supplied and preserved with LPDG solution for 120 minutes. In the study group 50 000 U/kg of ulinastatin was added to the LPDG solution for lung preservation. Then re-ventilation and reperfusion of the left lung were performed for 90 minutes. Blood gas analysis （PaO2, PaCO2）, mean pulmonary artery pressure （MPAP） and serum TNF-α level were measured intermittently. The pulmonary water index （D/W）, tissue myeloperoxidase （MPO） activity, tissue malondialdehyde （MDA） content and morphologic changes were *** The study group showed significantly higher PaO2 and lower MPAP at the end of reperfusion. Serum TNF-α level, left lung tissue MPO and MDA in the study group were significantly lower than those in the control group. D/W and pathologic evaluation were also remarkably different between the two *** This study indicated that better lung preservation could be achieved with the use of an ulinastatin modified LPDG solution. Ulinastatin further attenuated lung I/R injury, at least partly by reducing oxidative reactions,inhibiting the release of inflammatory factors and neutrophils immigration.

关键词： ischemia reperfusion injury organ preservation lung LPDG solution ulinastatin urinary trypsin inhibitor rabbits

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Lung preservation with ulinastatin-added-LPDG solution further attenuate ischemia-reperfusion injury in rabbits

Lung preservation with ulinastatin-added-LPDG solution furth...

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2009年浙江省麻醉学学术会议

作者： Department of Anesthesiology,College of Medicine,Zhejiang University, Hangzhou 310003,Zhejiang Province,China Ming Xu Xiaohong Wen Shuping Chen Xiaoxia An Heyun Xu,

Objectives lung protective solution is related to ischemia-reperfusion lung graft *** supposed that the addition of ulinastatin to LPDG as a flushing and preservation solution,would further ameliorate reperfusion ***:... 详细信息

关键词： ischemia reperfusion injury lung transplantation rabbit ulinastatin urinary trypsin inhibitor

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